苯托沙敏 | 92-12-6

• 物质功能分类: 原料药 - 抗变态反应药 - 抗组胺药
• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 苯托沙敏
• 中文别名: 4,6-二甲基异噁唑[5,4-b]吡啶-3-胺
• 英文名称: phenyltoloxamine
• 英文别名: 2-(2-benzylphenoxy)-N,N-dimethylethanamine；[2-(2-benzyl-phenoxy)-ethyl]-dimethyl-amine；[2-(2-Benzyl-phenoxy)-aethyl]-dimethyl-amin；2-Dimethylamino-1-(2-benzyl-phenoxy)-aethan；β-(Diethylamino)ethyl-o-benzylether
• CAS: 92-12-6
• 化学式: C₁₇H₂₁NO
• 分子量: 255.36
• InChiKey: IZRPKIZLIFYYKR-UHFFFAOYSA-N

物化性质

• 熔点：
  <25 °C
• 沸点：
  bp 141-144° (at <0.1 mm Hg)
• 密度：
  1.022±0.06 g/cm3(Predicted)
• 保留指数：
  1926;1926;1925;1960;1943.8;1927.4;1915;1915;1970;1938

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  19
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  12.5
• 氢给体数：
  0
• 氢受体数：
  2

ADMET

代谢

关于苯甲托品醇的代谢数据并不容易获得。实际上，许多第一代H1抗组胺药物从未对其药代动力学（即吸收、分布、代谢和排泄）进行过最佳研究。

Readily accessible data regarding the metabolism of phenyltoloxamine is not available. In fact, many first-generation H1 antihistamines have never had their pharmacokinetics (ie. absorption, distribution, metabolism, and elimination) optimally investigated.

来源:DrugBank

毒理性

• 肝毒性

像大多数第一代抗组胺药一样，苯托拉明并未与肝功能测试异常或临床明显的肝损伤有关联。其安全性可能与它的半衰期短和使用时限有关。 关于抗组胺药的安全性和潜在肝毒性的参考资料，在抗组胺药概述部分之后给出。 可能性评分：E（不太可能是临床明显肝损伤的原因）。 药物类别：抗组胺药

Like most first generation antihistamines, phenyltoloxamine has not been linked to liver test abnormalities or to clinically apparent liver injury. The reason for its safety may relate its short half-life and limited duration of use. References on the safety and potential hepatotoxicity of antihistamines are given together after the Overview section on Antihistamines. Likelihood score: E (unlikely to be a cause of clinically apparent liver injury). Drug Class: Antihistamines

来源:LiverTox

毒理性

• 蛋白质结合

关于苯甲托品与蛋白质结合的易于获取的数据并不存在。实际上，许多第一代H1抗组胺药从未对其药代动力学（即吸收、分布、代谢和排泄）进行过最佳研究。

Readily accessible data regarding the protein binding of phenyltoloxamine is not available. In fact, many first-generation H1 antihistamines have never had their pharmacokinetics (ie. absorption, distribution, metabolism, and elimination) optimally investigated.

来源:DrugBank

吸收、分配和排泄

• 吸收

关于苯乙托嗪的吸收数据并不容易获得。实际上，许多第一代H1抗组胺药物从未对其药代动力学（即吸收、分布、代谢和排泄）进行过最佳研究。

Readily accessible data regarding the absorption of phenyltoloxamine is not available. In fact, many first-generation H1 antihistamines have never had their pharmacokinetics (ie. absorption, distribution, metabolism, and elimination) optimally investigated.

来源:DrugBank

吸收、分配和排泄

• 消除途径

关于苯甲托品的主要消除途径的易于获取的数据并不存在。实际上，许多第一代H1抗组胺药从未对其药代动力学（即吸收、分布、代谢和排泄）进行过最佳研究。

Readily accessible data regarding the primary route of elimination of phenyltoloxamine is not available. In fact, many first-generation H1 antihistamines have never had their pharmacokinetics (ie. absorption, distribution, metabolism, and elimination) optimally investigated.

来源:DrugBank

吸收、分配和排泄

• 分布容积

关于苯甲托品醇的分布体积的数据并不容易获得。实际上，许多第一代H1抗组胺药从未对其药代动力学（即吸收、分布、代谢和排泄）进行过最佳研究。

Readily accessible data regarding the volume of distribution of phenyltoloxamine is not available. In fact, many first-generation H1 antihistamines have never had their pharmacokinetics (ie. absorption, distribution, metabolism, and elimination) optimally investigated.

来源:DrugBank

吸收、分配和排泄

• 清除

关于苯甲托品醇的清除数据并不容易获得。实际上，许多第一代H1抗组胺药物从未对其药代动力学（即吸收、分布、代谢和排泄）进行过最佳研究。

Readily accessible data regarding the clearance of phenyltoloxamine is not available. In fact, many first-generation H1 antihistamines have never had their pharmacokinetics (ie. absorption, distribution, metabolism, and elimination) optimally investigated.

来源:DrugBank

制备方法与用途

苯甲苯胺（Bistrimin）是一种具有镇静和镇痛作用的抗组胺药，同时还表现出强烈的与Sigma-1受体结合的能力（Ki: 160 nM）。

反应信息

• 作为反应物：
  描述：

  苯托沙敏 在 硫酸 、 溶剂黄146 、 铂 作用下， 60.0 ℃ 、343.21 kPa 条件下， 生成 Phenyltoloxamine
  参考文献：
  名称：

  苄基酚的烷基氨基烷基醚。

  摘要：

  DOI：

  10.1021/ja01169a017
• 作为产物：
  描述：

  苯甲基苯酚 在 偶氮二甲酸二异丙酯 、 potassium carbonate 、 三苯基膦 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 18.0h， 生成 苯托沙敏
  参考文献：
  名称：

  Dopamine/Serotonin Receptor Ligands. 9. Oxygen-Containing Midsized Heterocyclic Ring Systems and Nonrigidized Analogues. A Step toward Dopamine D₅ Receptor Selectivity

  摘要：

  Eleven-membered heterocycles (dibenz[g,j]-1-oxa-4-azacycloundecenes) and open-chain analogues were synthesized and investigated for affinities to human dopamine receptor subtypes. The moderately rigidized rings displayed nanomolar and sulmanomolar K-i values at D-1-like receptors with a significant D-1 to D-2 and a slight D-5 to D-6 selectivity. The open-chain analogues showed lower affinities but significant D-1 to D-2 selectivities. Compound 3 (K-i(D-5) = 0.57 nmol) showed antagonistic or inverse agonistic binding characteristics in a functional Ca assay.

  DOI：

  10.1021/jm049720x

文献信息

• [EN] SPIROLACTAM CGRP RECEPTOR ANTAGONISTS<br/>[FR] ANTAGONISTES DE RÉCEPTEUR DE CGRP À BASE DE SPIROLACTAME
  申请人：MERCK SHARP & DOHME

  公开号：WO2013169567A1

  公开（公告）日：2013-11-14

  The present invention is directed to spirolactam analogues which are antagonists of CGRP receptors and useful in the treatment or prevention of diseases in which CGRP is involved, such as migraine. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which CGRP is involved.

  本发明涉及螺内酰胺类似物，其为CGRP受体拮抗剂，可用于治疗或预防涉及CGRP的疾病，如偏头痛。该发明还涉及包含这些化合物的药物组合物，以及在预防或治疗涉及CGRP的这类疾病中使用这些化合物和组合物。
• [EN] IMIDAZOLINONE DERIVATIVES AS CGRP RECEPTOR ANTAGONISTS<br/>[FR] DÉRIVÉS D'IMIDAZOLINONE EN TANT QU'ANTAGONISTES DE RÉCEPTEURS CGRP
  申请人：MERCK SHARP & DOHME

  公开号：WO2010077752A1

  公开（公告）日：2010-07-08

  The present invention is directed to imidazolinone derivatives which are antagonists of CGRP receptors and useful in the treatment or prevention of diseases in which CGRP is involved, such as migraine. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which CGRP is involved.

  本发明涉及嘧啶啉酮衍生物，其为CGRP受体拮抗剂，可用于治疗或预防涉及CGRP的疾病，如偏头痛。该发明还涉及包含这些化合物的药物组合物，以及在预防或治疗涉及CGRP的这类疾病中使用这些化合物和组合物。
• [EN] INDAZOLOPYRIMIDINONES AS FIBRINOLYSIS INHIBITORS<br/>[FR] INDAZOLOPYRIMIDINONES COMME INHIBITEURS DE LA FIBRINOLYSE
  申请人：BAYER PHARMA AG

  公开号：WO2016173948A1

  公开（公告）日：2016-11-03

  The present application relates to novel substituted indazolopyrimidinones, to processes for their preparation, the compounds for use alone or in combinations in a method for the treatment and/or prophylaxis of diseases, in particular for the treatment and/or prophylaxis of acute and recurrent bleeding in patients with or without underlying hereditary or acquired hemostatic disorders, wherein the bleeding is associated with a disease or medical intervention selected from the group consisting of heavy menstrual bleeding, postpartum hemorrhage, hemorrhagic shock, trauma, surgery, transplantation, stroke, liver diseases, hereditary angioedema, nosebleed, and synovitis and cartilage damage following hemarthrosis.

  本申请涉及新型取代吲唑吡咯嘧啶酮，其制备方法，以及用于治疗和/或预防疾病的化合物，特别是用于治疗和/或预防患有或不患有基础遗传或获得性止血障碍的患者急性和复发性出血的方法，其中出血与从重经期出血、产后出血、出血性休克、创伤、手术、移植、中风、肝病、遗传性血管性水肿、鼻血、以及血液积聚后的滑膜炎和软骨损伤等一组疾病或医疗干预有关。
• [EN] DEUTERATED MORPHINE DERIVATIVES<br/>[FR] DÉRIVÉS DE MORPHINE DEUTÉRÉS
  申请人：SZEGEDI TUDOMÁNYEGYETEM

  公开号：WO2014170704A1

  公开（公告）日：2014-10-23

  The invention relates to new morphine derivatives deuterated at the 7,8-position of the morphine ring, furthermore to a process for the preparation thereof, and to pharmaceutical compositions comprising them. The new deuterated morphine derivatives show high and selective μ-opioid receptor binding activity leading to the benefit of higher analgesic activity at lower dosages inducing thereby reduced adverse effects compared to the hydrogenated derivatives. The compounds of the invention are useful for example in the treatment of pain or can be used as antitussive agents with a reduced risk of the possibility of drug abuse.

  这项发明涉及新的吗啡衍生物，其在吗啡环的7,8-位置被氘代取，此外还涉及其制备方法以及包含它们的药物组合物。这些新的氘代吗啡衍生物显示出高度和选择性的μ-阿片受体结合活性，从而在较低剂量下产生更高的镇痛活性，因此与氢化衍生物相比，减少了不良反应。该发明的化合物可用于例如治疗疼痛，或可用作镇咳剂，具有较低的药物滥用可能性。
• PIPERIDINONE CARBOXAMIDE AZAINDANE CGRP RECEPTOR ANTAGONISTS
  申请人：Bell Ian M.

  公开号：US20120122899A1

  公开（公告）日：2012-05-17

  The present invention is directed to piperidinone carboxamide azaindane derivatives which are antagonists of CGRP receptors and useful in the treatment or prevention of diseases in which the CGRP is involved, such as migraine. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which CGRP is involved.

  本发明涉及哌啶酮羧酰胺吖啶衍生物，它们是CGRP受体拮抗剂，可用于治疗或预防CGRP参与的疾病，如偏头痛。该发明还涉及包含这些化合物的药物组合物，以及在预防或治疗CGRP参与的这类疾病中使用这些化合物和组合物。

表征谱图